Efficacy and Safety of Pemafibrate, a Novel Selective PPARα Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial.

AIMS: Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. METHODS: A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. RESULTS: The percentage change in TG levels from baseline was -34.1%, -44.0%, -30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo (p＜0.0001) and fenofibrate groups (p=0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. CONCLUSIONS: In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.

Effectiveness of Low-Level Laser Therapy in Reducing Postoperative Pain After Dental Implant Surgery: A Randomized Clinical Trial.

BACKGROUND: A clinical trial was conducted to measure the effectiveness of a combined wavelength of 660 nm and 808 nm Low-Level Laser Therapy (LLLT) in reducing postoperative pain in partially and totally edentulous patients who underwent dental implant surgery. MATERIALS AND METHODS: The study included 20 blinded individuals divided in a randomized split-mouth fashion; the experimental group in one hemiarch and the control group in the other hemiarch. The experimental group received a total of 22.5 Joules (J) of LLLT divided into 5 points per implant immediately after surgery. The control group received a placebo treatment. At 24 hours, 72 hours, and 7 days, a blinded surveyor administered a pain questionnaire using a Numerical Rating Scale (NRS) combined with a Verbal Rating Scale (VRS) to assess pain onset after surgery, duration of the first pain episode, and pain evolution. Group data were analyzed with an ANOVA test for repeated measures and a paired t-test at defined time intervals. RESULTS: The experimental group showed a significant decrease in postoperative pain at 24 hours and at 72 hours for fully edentulous patients. There was a non-significant difference in the duration of the first pain episode. The mean pain levels decreased over time for both the experimental and control treatments, but only statistically significantly for the experimental group in the 24-72 hours and 24 hours to 7 days intervals. The same was true for the control group when comparing 24 and 72 hours and between 24 hours and 1 week. The time range between 72 hours and 1 week showed no statistically significant differences. CONCLUSION: Within the limitations of this study, a single dose of 22.5 J LLLT per implant helps to decrease postoperative pain in dental implant surgery at 24 hours for partially edentulous patients and at 24 and 72 hours for fully edentulous patients.

Placental cord drainage impact on third stage of labor: A randomized controlled trial.

BACKGROUND: The third stage of labor is a pivotal phase in obstetric care. Management may be physiological or active. Although the use of prophylactic placental cord drainage has been assessed in prior data, there is still no clear-cut evidence supporting its effectiveness in improving key obstetric outcomes. OBJECTIVE: The aim of the study was to investigate the impact of placental cord drainage during the third stage of labor on the amount of maternal bleeding, duration of the third stage, and incidence of postpartum hemorrhage. STUDY DESIGN: A randomized controlled trial was conducted at a high-volume tertiary obstetric center between May 2021 and December 2022. A total of 212 pregnant women with a singleton uncomplicated pregnancy were randomly assigned to undergo placental cord drainage or standard care without drainage. The randomization was manual, using pre-marked cards drawn by the participants. The power calculation determined a sample size of 92 participants per group to achieve 80% power at a 5% significance level, aiming to detect 20% difference in bleeding amount between the groups. In practice, we included more than 100 women in each group. The primary outcome was the amount of bleeding during the third stage of labor, while secondary outcomes included the duration of the third stage and incidence of postpartum hemorrhage. After delivery, all participants received 10 units of oxytocin via intravenous drip and delayed cord clamping was performed. In the study group, the maternal umbilical cord was then unclamped. Blood was allowed to drain into a plastic bag placed under the women's buttocks. If an episiotomy or perineal tear was observed, pressure packing was applied to reduce bleeding. The collected blood was measured in milliliters after placental expulsion. RESULTS: A total of 212 women were recruited of whom 104 underwent placental cord drainage and 108 received standard care without drainage. No significant differences were observed between the intervention and control groups in mean duration of the third stage of labor (10.56±6.12 vs. 10.95±6.33 minutes, P=0.65), incidence of postpartum hemorrhage (3.84% vs. 7.41%, P=0.38), or mean amount of bleeding during the third stage of labor (292±200 vs. 300±242 ml, P=0.79). Furthermore, there were no significant between-group differences in the mean amount of bleeding on separate analysis of nulliparous women (356±246 vs. 330±240 ml, P=0.68), multiparous women (265±171 vs. 289±244 ml, P=0.50), women who were not exposed to external oxytocin during labor (287±204 vs. 317±250 ml, P=0.59), and women who were exposed to external oxytocin (296±198 vs. 289±238 ml, P=0.39). CONCLUSIONS: Placental cord drainage during the third stage of labor showed no statistically significant impact on bleeding amount, third-stage length, or postpartum hemorrhage rate. The findings suggest that placental cord drainage may not offer additional benefits in preventing postpartum hemorrhage in women with uncomplicated pregnancies.

Obstetrics and Gynecologic Hospitalists and Their Focus: Impact on Safety and Quality Metrics.

Obstetrics and gynecologic hospitalists play a pivotal role in the evolution of perinatal care. Hospitalists improve patient safety by providing on-site, reliable, high-quality care. Hospitalists help to reduce the rates of unnecessary cesarean deliveries and increase the rates of vaginal deliveries.

[Network Meta-analysis of Chinese patent medicines in treatment of chronic pulmonary heart disease].

Network Meta-analysis was performed to compare the efficacy and safety of Chinese patent medicines in treating chronic pulmonary heart disease. CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of treating chronic pulmonary heart disease with Chinese patent medicines with the time interval from inception to December 2023. The Cochrane risk-of-bias tool was used for quality assessment of the included articles. RevMan 5.4 and Stata 17.0 were employed to establish the risk of bias map and perform the network Meta-analysis, respectively. Ultimately, a total of 95 RCTs involving 8 787 cases and 11 different Chinese patent medicines were included. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of cardiac function improves clinical total effective rate, SUCRA the top three were Wenxin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(2)For improving forced expiratory volume in the first se-cond(FEV1), SUCRA the top three were Danting Feixin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3)Regarding increasing the FEV1/forced vital capacity(FVC%) value, SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(4)In terms of increasing the partial pressure of oxygen(PaO_2), SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(5)In terms of reducing the partial pressure of carbon dioxide(PaCO_2), SUCRA the top three were Tongxinluo Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(6)In terms of increasing left ventricular ejection fraction(LVEF), SUCRA the top three were Bufei Huoxue Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(7)In terms of decreasing brain natriu-retic peptide(BNP), SUCRA the top three were Compound Danshen Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(8)In terms of improving the hematocrit level, SUCRA the top three were Qishen Yiqi Dropping Pills + conventional western medicine, Compound Danshen Dropping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine. In terms of safety, 26 RCTs reported adverse reactions, which primarily involved the circulatory and digestive systems. The combination of Chinese patent medicines with conventional western medicine has demonstrated enhanced therapeutic effects on chronic pulmonary heart disease. However, due to the varying quality and sample sizes of included studies and the absence of direct comparisons between Chinese patent medicines, the conclusions should be further validated by multicenter studies with larger sample sizes and higher methodological rigor.

Randomized controlled trial on the efficacy of a custom-made, fully guided implant system for flapless crestal sinus floor elevation: Accuracy and patient-reported outcomes.

OBJECTIVE: To compare fully guided flapless implant surgery using a light-cured surgical guide (FG group) with partially guided open flap surgery (PG group) in the posterior maxilla when performing simultaneous sinus floor elevation in terms of the accuracy, time requirements, and patient/clinician-reported outcomes (PROMs and CROMs). MATERIALS AND METHODS: In this study, 56 tissue-level implants were placed with crestal sinus floor elevation in 56 patients at single-tooth sites, with 28 implants allocated to the PG group and 28 to the FG group. The deviations of the placed implants from the virtually planned positions were measured at the implant platform and apex and for the angular deviation. The presurgical preparation time and the duration of surgery were measured. PROMs and CROMs were made by administering questionnaires at multiple time points. RESULTS: Horizontal deviations at the platform and apex and the angular deviation were significantly smaller in the FG group than the PG group (p < .05). Presurgical preparation and surgery times were significantly shorter in the FG group (p < .001). Patient satisfaction and willingness to receive repeat treatment were significantly better in the FG group than in the PG group (p < .005 and .025, respectively). Clinicians were more satisfied in the FG group than the PG group (p < .05). CONCLUSION: When placing an implant with sinus floor elevation, the flapless approach using a fully guided surgical system can be more accurate, faster, and increase the satisfaction of both the clinician and patient compared to the partially guided surgery.

Hip Arthroscopy Versus Physical Therapy for the Treatment of Symptomatic Acetabular Labral Tears in Patients Older Than 40 Years: 24-Month Results From a Randomized Controlled Trial.

BACKGROUND: The indications for hip arthroscopy in patients aged ≥40 years remain controversial, as observational studies have suggested that advanced age portends poor functional outcomes, poor durability of improvement, and high rates of conversion to total hip arthroplasty. PURPOSE: To compare hip arthroscopy versus nonoperative management for symptomatic labral tears in patients aged ≥40 years with limited radiographic osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This single-surgeon, parallel randomized controlled trial included patients aged ≥40 years with limited osteoarthritis (Tönnis grades 0-2) who were randomized 1:1 to arthroscopic surgery with postoperative physical therapy (SPT) or physical therapy alone (PTA). Patients who received PTA and achieved unsatisfactory improvement were permitted to cross over to SPT after completing ≥14 weeks of physical therapy (CO). The primary outcomes were the International Hip Outcome Tool-33 score and modified Harris Hip Score at 24 months after surgery, and secondary outcomes included other patient-reported outcome measures and the visual analog scale for pain. The primary analysis was performed on an intention-to-treat basis using linear mixed-effects models. Sensitivity analyses included modified as-treated and treatment-failure analyses. RESULTS: A total of 97 patients were included, with 52 (53.6%) patients in the SPT group and 45 (46.4%) patients in the PTA group. Of the patients who underwent PTA, 32 (71.1%) patients crossed over to arthroscopy at a mean of 5.10 months (SD, 3.3 months) after physical therapy initiation. In both intention-to-treat and modified as-treated analyses, the SPT group displayed superior mean patient-reported outcome measure and pain scores across the study period for nearly all metrics relative to the PTA group. In the treatment-failure analysis, the SPT and CO groups showed greater improvement across all metrics compared with PTA; however, post hoc analyses revealed no significant differences in improvement between the SPT and CO groups. No significant differences were observed between groups in rates of total hip arthroplasty conversion. CONCLUSION: In patients ≥40 years of age with limited osteoarthritis, hip arthroscopy with postoperative physical therapy led to better outcomes than PTA at a 24-month follow-up. However, additional preoperative physical therapy did not compromise surgical outcomes and allowed some patients to avoid surgery. When surgery is indicated, age ≥40 years should not be considered an independent contraindication to arthroscopic acetabular labral repair. REGISTRATION: NCT03909178 (ClinicalTrials.gov identifier).

The effects of N-acetyl cysteine on intrinsic functional connectivity and neural alcohol cue reactivity in treatment-seeking individuals with alcohol use disorder: a preliminary study.

N-acetyl cysteine (NAC) is a potential pharmacotherapy for alcohol use disorder (AUD), but it is not known whether it modulates neural activation to alcohol cues or intrinsic functional connectivity. We investigated whether NAC attenuates (i) alcohol cue-elicited activation, and (ii) intrinsic functional connectivity compared to placebo in patients with AUD. In this preliminary study, twenty-three individuals (7 females) with moderate-severe AUD received daily NAC (2400 mg/day, n = 9), or a placebo (n = 14) for at least 2 weeks. Participants completed a pre-treatment functional magnetic resonance imaging session (T0) and a post-treatment session (T1) comprising resting-state and visual alcohol cue reactivity task acquisitions. Activation differences between sessions, treatment, and session-by-treatment interaction were assessed. Resting-state functional connectivity examined using 377 node ROI-to-ROIs evaluated whether NAC reduced intrinsic functional connectivity after treatment. There were no differences in alcohol cue reactivity for brain activation or subjective craving between NAC and placebo during treatment or across sessions, or significant interaction. A significant treatment-by-time interaction, with reduced intrinsic connectivity was observed after treatment (T1) for NAC-treated compared to placebo-treated patients in the posterior cingulate node (9, left hemisphere) of the dorsal attentional network and connections to salience, ventral-attentional, somatosensory, and visual-peripheral networks implicated in AUD. NAC reduced intrinsic functional connectivity in patients with moderate-severe AUD after treatment compared to placebo, but did not attenuate alcohol cue-elicited activation. However, the absence of cue reactivity findings may result from low power, rather than the absence of cue reactivity findings associated with NAC. These results provide preliminary evidence that NAC treatment may modulate intrinsic functional connectivity brain activation in patients with alcohol use disorder, but replication in larger studies are required to determine the strength of this effect and any associations with clinical outcomes. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT03879759.

Effect of Face Masking on Transmission of SARS-CoV-2.

The efficacy of face masking for the public is not convincing to prevent the transmission of respiratory tract viruses such as SARS-CoV-2 when the criteria of evidence-based medicine are applied. This finding is mainly explained by the results from randomized-controlled trials (RCTs) when a high prevalence of the infection and a high compliance in mask wearing was assured. Throughout these studies no significant protective effect was observed. Observational studies with surgical masks describe a significant protective effect, but are prone to confounders such as physical distance. Respirators do not provide an additional health benefit compared to surgical or medical masks (RCTs). Community masks can even increase the risk of infection (RCTs). Based on the categories of evidence-based medicine, the efficacy results can best be categorized as conflicting evidence. Many relevant adverse events are described when masks are worn for hours such as dyspnea (12.2-52.8%), headache (3.9-73.4%), pruritus (0.0-60.0%), and skin reactions (0.0-85.0%). Their frequency is often higher with respirators. In future pandemics, masks should only be recommended or mandated for settings in which a clinically relevant health benefit can be expected, defined as the prevention of severe, critical or fatal disease, that clearly outweighs the expectable associated adverse reactions.

Single-arm, first-in-human feasibility study results for an ultra-low-cost insulin pump.

BACKGROUND: Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices. METHODS: This first-in-human feasibility study recruited six participants with T1D. During a nine-hour inpatient stay, participants used the ULCIP under clinical supervision. Venous glucose, insulin, and ß-Hydroxybutyrate were monitored to assess device performance. RESULTS: Participants displayed expected blood glucose and blood insulin levels in response to programmed basal and bolus insulin dosing. One participant developed mild ketosis, which was treated and did not recur when a new pump reservoir was placed. All other participants maintained ß-Hydroxybutyrate < 0.6 mmol/L throughout. CONCLUSION: The ULCIP safely delivered insulin therapy to users in a supervised inpatient environment. Future work should focus on correcting a pump hardware issue identified in this trial and extending device capabilities for use in closed loop control. Longer-term outpatient studies are warranted. TRIAL REGISTRATION: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623001288617) on the 11 December 2023.

WATSU (Water-Shiatsu) increases body awareness and improves pain and mood: A randomised controlled study.

BACKGROUND AND PURPOSE: WATSU (Water-Shiatsu) is a body-oriented therapy in warm-water pool with passive movements, massage and breathing techniques. The present study investigated the short-term effect of a single session of WATSU on body awareness. MATERIALS AND METHODS: In a randomized-controlled study 60 volunteers (18-65 years) were assigned to a 20-min intervention of WATSU or to a 20-min lecture on WATSU. Immediately before and after the intervention they had to answer questionnaires. Primary endpoint of the investigation was the change of the total score of the non-verbal Awareness Body Chart (ABC). Secondary endpoints were the changes of the scores of the 14 single body parts of the ABC, of the Visual Analogue Pain Scale, of a German self-perception questionnaire (KEKS) and changes in mood scored with a German questionnaire on mood (Bf-SR). To compare groups, Mann-Whitney U tests were used. RESULTS: The WATSU group had a significantly higher increase in the ABC total score in comparison to the lecture group (WATSU: 0.3 (IQR 0 - 0.8), lecture: 0.1 (IQR -0.2 - 0.2), p = 0.014). In the KEKS no group differences were seen. In WATSU a significantly stronger improvement of pain (Visual Analogue Pain Scale: WATSU: -15 (IQR -29 to -8), lecture: -4 (IQR -9 - 2), p < 0.001) and of mood (Bf-SR: WATSU: -6 (IQR -14 to -2), lecture: -1 (IQR -5 - 1), p = 0.003) could be observed. CONCLUSION: This study showed that WATSU immediately increases body awareness and improves pain and mood.

A case management strategy to reduce falls in older people with a history of falls: A randomized controlled trial.

The present study aimed to determine whether a remotely delivered intervention, based on an individual case management, can reduce falls and their consequences in community-dwelling older people with a history of multiple falls. In this randomized controlled trial, 32 participants were randomized to the intervention group, which comprised a 16-week case management program involving a multidimensional assessment, targeted interventions according to the identified fall risk factors, and development of individualized care plans. The intervention was performed by trained gerontologists, under weekly supervision of professionals with experience in falls. The control group (n = 30) received usual care. Falls were monitored over 12 months with monthly falls calendars and telephone calls. Remotely delivered case management presented an 82 % uptake of recommendations. There was a trend toward a reduced fall incidence in the intervention vs control group, with lower fall, fall injury and fracture rates in the intervention group compared with the control group at both the 16-week and 12-month time-points, with the difference statistically significant for injurious fall rates at 12 months - IRR=0.18 (95 % CI = 0.04 to 0.74).

Vaginal dinoprostone versus Foley catheter for induction of labor at term with an unfavorable cervix: an open-label randomized controlled trial.

BACKGROUND: Induction of labor with mechanical methods or pharmacological agents is used in about 20-30% of all pregnant women. We specialized in comparing the effectiveness and safety of dinoprostone versus transcervical Foley catheter for induction of labor in term pregnant women with an unfavorable cervix with adequate samples. OBJECTIVE: To compare the effectiveness and safety of dinoprostone versus transcervical Foley catheter for induction of labor in term pregnant women with an unfavorable cervix. STUDY DESIGN: This is a parallel, open-label randomized controlled trial in two maternal centers in Shanghai, China between October 2019 and July 2022. Women with a singleton pregnancy in cephalic presentation at term and an unfavorable cervix (Bishop score < 6) scheduled for induction of labor were eligible. 1,860 women were randomly allocated to cervical ripening with either a dinoprostone vaginal insert (10mg) or a 60cc Foley catheter for up to 24 hours. The primary outcomes were vaginal delivery rate and time to vaginal delivery. Secondary outcomes included time to delivery and maternal and neonatal morbidity. Analysis was done from an intention-to-treat perspective. The trial was registered with the China trial registry (CTR2000038435). RESULTS: The vaginal birth rates were 72.8% (677/930) vs. 69.9% (650/930) in vaginal dinoprostone and Foley catheter, respectively (aRR 1.04, 95% CI 0.98 to 1.10, risk difference: 0.03). Time to vaginal delivery was not significantly different between the two groups (sub-distribution hazard ratio 1.11, 95% CI 0.99-1.24). Vaginal dinoprostone was more likely complicated with hyperstimulation with fetal heart rate changes (5.8% vs. 2.8%, aRR 2.09, 95% CI 1.32-3.31) and placenta abruption (0.9% vs. 0.1%, aRR: 8.04, 95% CI 1.01-64.15), while Foley catheter was more likely complicated with suspected intrapartum infection (5.1% vs. 8.2 %, aRR: 0.62, 95% CI 0.44-0.88) and postpartum infection (1.4% vs. 3.7%, aRR: 0.38, 95% CI 0.20-0.72). The composite of poor neonatal outcomes was not significantly different between the two groups (4.5% vs. 3.8%, aRR 1.21, 95% CI 0.78 to 1.88), while more neonatal asphyxia occurred in the dinoprostone group (1.2% vs. 0.2%, aRR 5.39, 95% CI 1.22 to 23.92). In a subgroup analysis, vaginal dinoprostone decreased vaginal birth rate slightly in multiparous women (90.6% vs. 97.0%, aRR 0.93, 95% CI 0.88 to 0.99). CONCLUSIONS: In term pregnant women with an unfavorable cervix, induction of labor with vaginal dinoprostone or Foley catheter has similar effectiveness. Foley catheter leads to better safety for neonates, while it may result in a higher risk of maternal infection. Furthermore, Foley catheter should be preferred in multiparous women.

First-Line Treatment with Atezolizumab plus Bevacizumab and Chemotherapy for US Patients with Metastatic, Persistent, or Recurrent Cervical Cancer: A Cost-Effectiveness Analysis.

OBJECTIVE: The BETAcc clinical trial demonstrated that chemotherapy combined with bevacizumab plus atezolizumab (CBA) significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with metastatic, persistent, or recurrent cervical cancer. However, to our knowledge, the economic value of using this new therapy for this indication is currently unknown. Therefore, our study aims to evaluate the cost-effectiveness of CBA for the first-line treatment of metastatic, persistent, or recurrent cervical cancer from the United States healthcare payers perspective. METHODS: A state-transition Markov model over a 10-year lifetime horizon was developed to compare the cost and effectiveness of CBA versus chemotherapy plus bevacizumab (CB). The primary outcomes of our study included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. RESULTS: CBA was associated with an additional 0.58 QALY at an extra cost of $172,495.90 compared to CB. The ICER was $295,972.43/QALY, significantly higher than the willingness-to-pay (WTP) threshold value of $150,000/QALY. One-way sensitivity analyses revealed that results were most sensitive to the PFD utility, the unit cost of atezolizumab, and PD utility. Probabilistic sensitivity analysis indicated that CBA achieved a 4.3% probability of cost-effectiveness at a $150,000/QALY threshold. To achieve cost-effectiveness, the unit price of atezolizumab must be reduced by approximately 56.6%. CONCLUSIONS: CBA treatment is unlikely to be a cost-effective option compared with CB for patients with persistent, recurrent, or metastatic cervical cancer in the United States.

Effects of a prenatal anxiety randomized controlled trial intervention on infant development in Pakistan.

OBJECTIVES: Given that infant development is influenced by caregiver mental health, we tested whether an intervention to reduce antenatal anxiety could affect infant development. A secondary aim was to test depressive symptoms, maternal responsiveness, and maternal infant bonding as mediators of this relationship. METHODS: Between 2020 and 2022, pregnant women participated in a randomized controlled trial of the Happy Mother-Healthy Baby (HMHB) program based on cognitive behavioral therapy. We collected data on child development from 202 intervention and 198 control participants in a public hospital in Pakistan. Child development was measured using the Ages and Stages Questionnaires-Version 3 at six weeks postpartum. Using intent-to-treat analyses, we examined whether the intervention was associated with performance on the five ASQ-3 domains. Causal mediation analysis was used to assess depressive symptoms, bonding, and maternal-infant responsiveness as mediators. RESULTS: Socio-demographic characteristics were evenly distributed between study arms. Intervention arm infants showed a 2.1-point increase (95% CI: 0.12, 4.17) in communication scores compared to controls. Though not achieving statistical significance, intervention infants also showed a 2.0-point increase (95% CI:-0.06, 4.09) in gross motor development performance. Bonding, depression, and responsiveness were mediators between the intervention and infant communication (Bindirect=1.94 (95%CI: 0.86, 3.25) depression; Bindirect=0.57 (95% CI: 0.09, 1.16) bonding; Bindirect=0.53 (95% CI: 0.01, 1.21) responsiveness; and Bindirect=1.94 (95%CI: 0.86, 3.25). Bonding, responsiveness, and depression mediated 25%, 23%, and 87% of the total association, respectively. CONCLUSIONS: HMHB positively affected infant communication at six-week follow-up. Larger studies with longer follow-up are needed to confirm and extend these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03880032; https://clinicaltrials.gov/ct2/show/NCT03880032.

Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma.

BACKGROUND: Mepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. OBJECTIVE: Our study aimed to explore the corticosteroid-responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway. METHOD: The MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for SEA. We analysed paired sputum (n=16) and plasma (n=25) samples from the MAPLE trial using high-throughput Olink® proteomics. We also analysed additional sputum proteins using ELISA. RESULTS: In patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type-2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated. Type-2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. CONCLUSION: At stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations.

Fascia Iliaca Block Combined with Low-dose Spinal Anesthesia for Hip Fracture Surgery in the Elderly: Effects on Severe Hypotension and Analgesia. A Randomized Controlled Trial.

BACKGROUND: Hip fracture surgeries in elderly patients often require spinal or general anesthesia, posing risks of severe hypotension and inadequate pain management. The optimal anesthesia type for minimizing these risks remains undetermined. Preliminary studies suggest that a combination of fascia iliaca block (FIB) and low-dose low-specific-gravity spinal anesthesia (LLSA) might offer a solution, but comprehensive evidence is lacking. OBJECTIVES: This study aimed to assess the efficacy of combining FIB with LLSA for reducing severe hypotension and enhancing analgesia during hip fracture surgery in elderly patients. STUDY DESIGN: A prospective, randomized controlled trial was conducted. SETTING: An operating theatre of a tertiary hospital. METHODS: The study comprised 68 patients. They were separated into 2 equal parallel groups 34 patients each: the FIB+LLSA group and the general anesthesia (GA) group. Patients aged 75-96 undergoing primary hip arthroplasty for hip fracture were randomized to receive either FIB+LLSA or GA. The primary outcome was the incidence of severe hypotension; secondary outcomes included postoperative pain, use of rescue analgesia, vasopressor dosage, and complications. RESULTS: We found a significantly lower incidence of severe hypotension in the FIB+LLSA group compared to the GA group (32.4% vs 67.6%). Additionally, postoperative pain scores were significantly lower, and the need for rescue analgesia was reduced in the FIB+LLSA group. Vasopressor use during surgery was also significantly lower in the FIB+LLSA group. The hospital stay was shorter in the FIB+LLSA group, with an average of 5.9 days compared to 6.7 days in the GA group. LIMITATIONS: The study's limitations include its single-center nature, which may limit the generalizability of the findings. Additionally, the inability to conduct a double-blind study could introduce biases, though measures were taken to minimize this. The sample size might not be sufficient to determine the broader implications of LLSA. CONCLUSIONS: Combining FIB with LLSA for elderly patients undergoing hip fracture surgery significantly reduces the incidence of severe intraoperative hypotension and postoperative pain. It also decreases the need for rescue analgesia and shortens hospital stays, suggesting that FIB+LLSA could be a beneficial regional anesthesia technique for elderly hip fracture surgery patients, aligning with enhanced recovery protocols.

Effects of ultrasound-guided thoracolumbar interfascial plane block combined with general anaesthesia versus general anaesthesia alone on emergence agitation in children with cerebral palsy undergoing selective posterior rhizotomy: protocol for a randomised controlled clinical trial.

INTRODUCTION: Selective posterior rhizotomy (SPR) is a preferred procedure for relieving spastic children with cerebral palsy, but it is associated with severe pain and significant emergence agitation (EA). The thoracolumbar interfascial plane (TLIP) block provides an effective blockade to the dorsal branch of the spinal nerve. We hypothesise that the TLIP block may be an effective tool to alleviate EA and postoperative pain scores in children with cerebral palsy undergoing SPR. METHODS AND ANALYSIS: This study is a single-centre, randomised, parallel-controlled trial being conducted in Beijing, China. A total of 50 paediatric patients with cerebral palsy scheduled for SPR are randomised in a 1:1 ratio to receive bilateral TLIP block with 0.2% ropivacaine 0.5 mL/kg or control. Patients in the TLIP group receive general anaesthesia combined with TLIP block, while patients in the control group receive only general anaesthesia, without a TLIP block. The primary outcome is the Paediatric Anaesthesia Emergence Delirium Score. The secondary outcomes are the incidence of EA, the Wong-Baker Faces Pain-rating Scale, the perioperative haemodynamics, the intraoperative remifentanil and propofol dosage, the extubation time and recovery time, and adverse reactions. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Dongzhimen Hospital, Beijing University of Chinese Medicine on 21 September 2023 (2023DZMEC-379-02). Written informed consent is obtained from the legal guardian of each patient. The results of this study will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: ChiCTR2300076397.

Alveolar Ridge Preservation Using a Collagenated Xenograft: A Randomized Clinical Trial.

OBJECTIVES: This study sought to evaluate the efficacy of cancellous bovine bone mineral granules and 10% porcine collagen (deproteinized bovine bone mineral with collagen [DBBM-C]; (OCS-B Collagen® [Straumann XenoFlex], NIBEC, Korea) in a mouldable block form, with or without socket seal, using autogenous free gingival graft (FGG). METHODS: Fifty-four patients were included and randomly assigned to one of three groups: (1) spontaneous healing (control group), (2) alveolar ridge preservation (ARP) using DBBM-C (DBBM-C group), and (3) ARP employing DBBM-C sealed with FGG (DBBM-C/FGG group). Bone biopsy and implant fixture placement were performed 180 days after ARP. Cone-beam computed tomography, histological analysis, implant stability, and three-dimensional volumetric analysis were conducted. RESULTS: Of the 54 patients, 4 dropped out owing to loss of follow-up and osseointegration failure. The changes in alveolar bone during follow-up were not significantly different. Between 84- and 180-day postextraction, the volume of the DBBM-C and DBBM-C/FGG groups was maintained at 3 mm below the alveolar ridge crest (0.72 ± 0.80 mm, 6.05 ± 6.69%), whereas the volume in the control group decreased (-0.37 ± 1.31 mm, -2.10% ± 8.37%) (P = .026). The DBBM-C/FGG group exhibited less horizontal ridge resorption at 1 mm below the alveolar crest (-9.19 ± 5.09 mm, -73.67% ± 32.53%) between preextraction and 84 days postextraction (P = .049). In all groups, the implant stability quotient remained above 70. CONCLUSIONS: Within the limitations of this study, both ARP using DBBM-C with and without socket sealing effectively preserved the width dimension of the alveolar ridge, with no significant difference in alveolar bone resorption. However, socket sealing appeared to enhance the stability of the bone graft and bone quality. CLINICAL RELEVANCE: The use of DBBM-C for ARP seems to aid in volume maintenance as compared with spontaneous healing. Gingival sealing with an FGG can help maintain the width of the alveolar ridge. This clinical trial was not registered prior to participant recruitment and randomization. This study was registered at WHO ICTRP (https://trialsearch.who.int/Trial2.aspx?TrialID=KCT0008266).